Trial record 1 of 2 for: RETHINC

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RETHINC: REdefining THerapy In Early COPD for the Pulmonary Trials Cooperative (RETHINC)

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ClinicalTrials.gov Identifier: NCT02867761

Recruitment Status : Completed

First Posted : August 16, 2016

Results First Posted : August 30, 2022

Last Update Posted : April 13, 2023

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Sponsor:

Collaborator:

National Heart, Lung, and Blood Institute (NHLBI)

Information provided by (Responsible Party):

MeiLan Han, University of Michigan

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	COPD (Chronic Obstructive Pulmonary Disease)
Interventions	Drug: Indacaterol/Glycopyrrolate Drug: Placebo
Enrollment	780

Participant Flow

Recruitment Details
Pre-assignment Details	Of the 780 consented, 242 were screen fails and 3 dropped out before randomization, so 535 were randomized.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Period Title: Overall Study
Started	261	274
Completed	233	248
Not Completed	28	26
Reason Not Completed
Participant withdrawn by investigator	0	1
Lost to Follow-up	25	18
Unable to complete protocol	3	7

Baseline Characteristics

Arm/Group Title		Indacaterol/Glycopyrrolate	Placebo	Total
Arm/Group Description		indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...	Total of all reporting groups
Arm/Group Description		indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo	Total of all reporting groups
Overall Number of Baseline Participants		261	274	535
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	261 participants	274 participants	535 participants
		58.6 (9.6)	59.1 (9.8)	58.8 (9.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	261 participants	274 participants	535 participants
	Female	134 51.3%	140 51.1%	274 51.2%
	Male	127 48.7%	134 48.9%	261 48.8%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	261 participants	274 participants	535 participants
	Hispanic or Latino	25 9.6%	22 8.0%	47 8.8%
	Not Hispanic or Latino	236 90.4%	252 92.0%	488 91.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	261 participants	274 participants	535 participants
	American Indian or Alaska Native	2 0.8%	1 0.4%	3 0.6%
	Asian	1 0.4%	1 0.4%	2 0.4%
	Native Hawaiian or Other Pacific Islander	0 0.0%	2 0.7%	2 0.4%
	Black or African American	92 35.2%	99 36.1%	191 35.7%
	White	148 56.7%	154 56.2%	302 56.4%
	More than one race	7 2.7%	5 1.8%	12 2.2%
	Unknown or Not Reported	11 4.2%	12 4.4%	23 4.3%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	261 participants	274 participants	535 participants
United States		261	274	535
COPD Assessment Test (CAT) Score ^[1] Mean (Standard Deviation) Unit of measure: Units on a scale
	Number Analyzed	261 participants	274 participants	535 participants
		17.5 (6.7)	17.6 (6)	17.6 (6.4)
		[1] Measure Description: 0 - 40; 0 as low symptoms (feeling better) and 40 as high symptoms (feeling worse)
St. George's Respiratory Questionnaire (SGRQ) Score ^[1] Mean (Standard Deviation) Unit of measure: Units on a scale
	Number Analyzed	261 participants	274 participants	535 participants
		37.9 (21)	38.4 (19.3)	38.2 (20.2)
		[1] Measure Description: 0 - 100 score; 0 as low symptoms (feeling better) and 100 as high symptoms (feeling worse)
Post bronchodilator FEV1 percent predicted Mean (Standard Deviation) Unit of measure: Percent predicted
	Number Analyzed	261 participants	274 participants	535 participants
		93.8 (14.0)	94.9 (12.6)	94.2 (13.3)

Outcome Measures

1.Primary Outcome


Title	Proportion (Percentage) of Individuals Who Experience a 4 Unit Improvement in St. George's Respiratory Questionnaire (SGRQ) at 12 Weeks and do Not Meet Criteria for Treatment Failure During the 12 Week Treatment Period
Description	Measured by units of improvement in SGRQ scores at Baseline and 12 wee...
Description	Measured by units of improvement in SGRQ scores at Baseline and 12 weeks, as well as review of treatment failure status at 4 weeks and 12 weeks of treatment (treatment failure is defined by an increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilator, corticosteroids or antibiotics). A 4 unit change is the minimum clinically important difference. SGRQ has a 0 - 100 score; 0 as low symptoms (feeling better) and 100 as high symptoms (feeling worse).
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

In the treatment arm, 5 subjects had primary efficacy assessment >=4 weeks after the last visit that were not included in the mITT (233 - 5 = 228). One additional subject was missing SGRQ at final visit (228 - 1 = 227). In the placebo arm, 5 subjects had primary efficacy assessment >=4 weeks after the last visit that were not included in the mITT (248 - 5 = 243). An additional person did not complete final visit but had treatment failure so are still included in mITT (243 + 1 = 244).


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	227	244
Measure Type: Count of Participants Unit of Measure: Participants
	128 56.4%	144 59.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.65
	Comments	[Not Specified]
	Method	Generalized Estimating Equation
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95% 0.60 to 1.37
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Proportion of Individuals With a 2 Unit Improvement in CAT Without Treatment Failure
Description	Proportion of individuals with a 2 unit improvement in CAT without tre...
Description	Proportion of individuals with a 2 unit improvement in CAT without treatment failure
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	227	244
Measure Type: Count of Participants Unit of Measure: Participants
	169 74.4%	166 68.0%

3.Secondary Outcome


Title	Proportion of Individuals With a 1 Unit Improvement in the BDI/TDI Without Treatment Failure
Description	Proportion of individuals with a 1 unit improvement in the BDI/TDI wit...
Description	Proportion of individuals with a 1 unit improvement in the BDI/TDI without treatment failure
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Not all participants had all measures measured.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	220	234
Measure Type: Count of Participants Unit of Measure: Participants
	80 36.4%	80 34.2%

4.Secondary Outcome


Title	Proportion of Individuals With Both a 4 Unit Improvement in SGRQ and a 1 Unit Improvement in BDI/TDI Without Treatment Failure
Description	Measured by units of improvement in SGRQ scores at Baseline and 12 wee...
Description	Measured by units of improvement in SGRQ scores at Baseline and 12 weeks, as well as review of treatment failure status at 4 weeks and 12 weeks of treatment (treatment failure is defined by an increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilator, corticosteroids or antibiotics).
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

Not all participants had all measures measured.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	220	234
Measure Type: Count of Participants Unit of Measure: Participants
	55 25.0%	60 25.6%

5.Secondary Outcome


Title	Mean Change in St. George's Respiratory Questionnaire (SGRQ)
Description	Value at 12 Weeks Minus Baseline. SGRQ has a 0 - 100 score; 0 as low s...
Description	Value at 12 Weeks Minus Baseline. SGRQ has a 0 - 100 score; 0 as low symptoms (feeling better) and 100 as high symptoms (feeling worse).
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	227	243
Mean (95% Confidence Interval) Unit of Measure: score on a scale
	-7.7 (-9.4 to -5.9)	-8.9 (-10.6 to -7.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.30
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

6.Secondary Outcome


Title	Mean Change in COPD Assessment Test (CAT)
Description	Value at 12 Weeks Minus Baseline. 0 - 40; 0 as low symptoms (feeling b...
Description	Value at 12 Weeks Minus Baseline. 0 - 40; 0 as low symptoms (feeling better) and 40 as high symptoms (feeling worse).
Time Frame	Baseline, 12 weeks

Outcome Measure Data

Analysis Population Description

In the treatment arm, 5 subjects had primary efficacy assessment >=4 weeks after the last visit that were not included in the mITT (233 - 5 = 228). One additional subject was missing CAT at final visit (228 - 1 = 227). In the placebo arm, 5 subjects had primary efficacy assessment >=4 weeks after the last visit that were not included in the mITT (248 - 5 = 243).


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	227	243
Mean (95% Confidence Interval) Unit of Measure: score on a scale
	-4.5 (-5.4 to -3.5)	-4.8 (-5.8 to -3.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.49
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

7.Secondary Outcome


Title	Mean Change in Baseline Dyspnea Index (BDI)/Transition Dyspnea Index (TDI)
Description	Value at 12 Weeks Minus Baseline.
Description	Value at 12 Weeks Minus Baseline.
Time Frame	12 Weeks

Outcome Measure Data

Analysis Population Description

Not all participants had these measures taken.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	219	233
Mean (95% Confidence Interval) Unit of Measure: ratio
	0.93 (0.59 to 1.27)	0.92 (0.59 to 1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.96
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

8.Secondary Outcome


Title	Area Under the Curve (AUC) 0-3 Hours for FEV1
Description	FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from...
Description	FEV1 AUC0-3h was calculated as the area under the FEV1-time curve from 0 to 3h post-dose using the trapezoidal rule, divided by the duration (3h) to report in liters.
Time Frame	At 12 weeks, FEV1 is measured at 1-hour intervals for 3 hours

Outcome Measure Data

Analysis Population Description

Not all persons completed their lung function tests.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	175	199
Mean (95% Confidence Interval) Unit of Measure: liters
	8.09 (7.99 to 8.20)	7.82 (7.72 to 7.92)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

9.Secondary Outcome


Title	Change From Baseline in Trough Forced Expiratory Volume Per 1 Second (FEV1) - Absolute Value
Description	Trough FEV1 at 12 week minus trough FEV1 at baseline.
Description	Trough FEV1 at 12 week minus trough FEV1 at baseline.
Time Frame	Baseline to 12 Weeks

Outcome Measure Data

Analysis Population Description

Not all participants had all measures measured.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	198	205
Least Squares Mean (95% Confidence Interval) Unit of Measure: Liters
	0.04 (0.01 to 0.08)	-0.01 (-0.04 to 0.02)

10.Secondary Outcome


Title	Change From Baseline in 12 Hour Trough Inspiratory Capacity - Absolute Value
Description	Change from baseline in 12 hour trough inspiratory capacity - absolute...
Description	Change from baseline in 12 hour trough inspiratory capacity - absolute value
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Not all participants had all measures measured.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	194	203
Least Squares Mean (95% Confidence Interval) Unit of Measure: Liters
	0.12 (0.07 to 0.18)	0.02 (-0.03 to 0.08)

11.Secondary Outcome


Title	Symptoms and Rescue Medication Use Based on Daily Diary
Description	Percentage of days with symptoms (shortness of breath, chest tightness...
Description	Percentage of days with symptoms (shortness of breath, chest tightness, wheezing, cough, or sputum) or use of albuterol
Time Frame	During study follow-up (Baseline to 12 weeks)

Outcome Measure Data

Analysis Population Description

Not all participants submitted complete diaries.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	198	210
Mean (95% Confidence Interval) Unit of Measure: percentage of days
	67.0 (59.0 to 75.0)	63.6 (55.7 to 71.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	P Value for percentage of days with any symptoms (shortness of breath, chest tightness, wheezing, cough, or sputum)
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.35
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	P Value for percentage of days with shortness of breath
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.61
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	P Value for percentage of days with chest tightness
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.48
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	P Value for percentage of days with wheezing
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.81
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	P Value for percentage of days with cough
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.17
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	P Value for percentage of days with sputum
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.64
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Indacaterol/Glycopyrrolate, Placebo
	Comments	P Value for percentage of days with use of albuterol.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.84
	Comments	[Not Specified]
	Method	Linear Mixed Effects Model
	Comments	[Not Specified]

12.Secondary Outcome


Title	Treatment Failure Defined by Increase in Lower Respiratory Symptoms Necessitating Treatment With Active, Long-acting Inhaled Bronchodilator, Corticosteroids or Antibiotics
Description	Treatment failure defined by increase in lower respiratory symptoms ne...
Description	Treatment failure defined by increase in lower respiratory symptoms necessitating treatment with active, long-acting inhaled bronchodilator, corticosteroids or antibiotics
Time Frame	During study follow-up (baseline to 12 Weeks)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	227	244
Measure Type: Count of Participants Unit of Measure: Participants
	5 2.2%	9 3.7%

13.Secondary Outcome


Title	Change From Baseline in Trough FEV1 - % Predicted
Description	Trough FEV1 at 12 week minus trough FEV1 at baseline.
Description	Trough FEV1 at 12 week minus trough FEV1 at baseline.
Time Frame	Baseline to 12 Weeks

Outcome Measure Data

Analysis Population Description

Not all participants had all measures measured.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	198	205
Least Squares Mean (95% Confidence Interval) Unit of Measure: percentage of predicted number
	2.48 (1.49 to 3.47)	-0.09 (-1.06 to 0.89)

14.Secondary Outcome


Title	Change in FEF25-75%
Description	FEF25-75%-Forced expiratory flow over the middle one half of the FVC; ...
Description	FEF25-75%-Forced expiratory flow over the middle one half of the FVC; the average flow from the point at which 25 percent of the FVC has been exhaled to the point at which 75 percent of the FVC has been exhaled.
Time Frame	Baseline to 12 weeks

Outcome Measure Data

Analysis Population Description

Not all participants had pulmonary function tests.


Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description:	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
Overall Number of Participants Analyzed	198	205
Mean (95% Confidence Interval) Unit of Measure: Liters per second
	0.07 (0.00 to 0.15)	-0.08 (-0.15 to 0.00)

Adverse Events

Time Frame	During the trial, approximately 12 weeks.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Indacaterol/Glycopyrrolate	Placebo
Arm/Group Description	indacaterol/glycopyrrolate 27.5/15....	Placebo 27.5/15.6 mcg inhaled twice...
Arm/Group Description	indacaterol/glycopyrrolate 27.5/15.6 mcg inhaled twice daily for 12 weeks Indacaterol/Glycopyrrolate: 27.5/15.6 mcg active indacaterol/glycopyrrolate	Placebo 27.5/15.6 mcg inhaled twice daily for 12 weeks Placebo: 27.5/15.6 mcg placebo
All-Cause Mortality
	Indacaterol/Glycopyrrolate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/261 (0.00%)	0/274 (0.00%)
Serious Adverse Events Serious Adverse Events
	Indacaterol/Glycopyrrolate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/261 (1.53%)	8/274 (2.92%)
Cardiac disorders
Chest Pain ^†	1/261 (0.38%)	0/274 (0.00%)
Gastrointestinal disorders
Abdominal Pain ^†	1/261 (0.38%)	1/274 (0.36%)
Anastomotic Ulcer ^†	1/261 (0.38%)	0/274 (0.00%)
Gastric GJ junction ulcer and posterior wall perforation ^†	1/261 (0.38%)	0/274 (0.00%)
Postprocedural Intraabdominal Abscess ^†	1/261 (0.38%)	0/274 (0.00%)
Sigmoid diverticulitis with small abscess ^†	0/261 (0.00%)	1/274 (0.36%)
Diarrhea ^†	1/261 (0.38%)	0/274 (0.00%)
Acute Cholecystitis ^†	1/261 (0.38%)	0/274 (0.00%)
Acute Pancreatitis ^†	0/261 (0.00%)	1/274 (0.36%)
Portal Hypertension ^†	0/261 (0.00%)	1/274 (0.36%)
Musculoskeletal and connective tissue disorders
Motor Vehicle Accident ^†	1/261 (0.38%)	1/274 (0.36%)
Non-displaced Fibular Fracture ^†	0/261 (0.00%)	1/274 (0.36%)
Psychiatric disorders
Breakthrough Seizures ^†	1/261 (0.38%)	0/274 (0.00%)
Suicide Attempt ^†	1/261 (0.38%)	0/274 (0.00%)
Uncontrolled hypertension ^†	0/261 (0.00%)	1/274 (0.36%)
Vitamin B12 Deficiency ^†	0/261 (0.00%)	1/274 (0.36%)
Renal and urinary disorders
Kidney stone with obstruction ^†	0/261 (0.00%)	1/274 (0.36%)
Respiratory, thoracic and mediastinal disorders
Respiratory Exacerbation ^†	0/261 (0.00%)	1/274 (0.36%)
Community Acquired Pneumonia ^†	0/261 (0.00%)	1/274 (0.36%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Indacaterol/Glycopyrrolate	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/261 (0.00%)	0/274 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

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Name/Title:	Meilan K. Han
Organization:	University of Michigan
Phone:	734 615-9772
EMail:	mrking@med.umich.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Han MK, Ye W, Wang D, White E, Arjomandi M, Barjaktarevic IZ, Brown SA, Buhr RG, Comellas AP, Cooper CB, Criner GJ, Dransfield MT, Drescher F, Folz RJ, Hansel NN, Kalhan R, Kaner RJ, Kanner RE, Krishnan JA, Lazarus SC, Maddipati V, Martinez FJ, Mathews A, Meldrum C, McEvoy C, Nyunoya T, Rogers L, Stringer WW, Wendt CH, Wise RA, Wisniewski SR, Sciurba FC, Woodruff PG; RETHINC Study Group. Bronchodilators in Tobacco-Exposed Persons with Symptoms and Preserved Lung Function. N Engl J Med. 2022 Sep 29;387(13):1173-1184. doi: 10.1056/NEJMoa2204752. Epub 2022 Sep 4.

Layout table for additonal information

Responsible Party:	MeiLan Han, University of Michigan
ClinicalTrials.gov Identifier:	NCT02867761
Other Study ID Numbers:	1U01HL128952-01 ( U.S. NIH Grant/Contract ) 1U01HL128952 ( U.S. NIH Grant/Contract )
First Submitted:	August 12, 2016
First Posted:	August 16, 2016
Results First Submitted:	July 7, 2022
Results First Posted:	August 30, 2022
Last Update Posted:	April 13, 2023

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